TCR transgenic mice in which usage of transgenic α- and β-chains is highly dependent on the level of selecting ligand

We have produced a TCR transgenic mouse that uses a TCR derived from a Thl clone that is specific for residues 64 to 76 of the d allele of murine hemoglobin presented by I-E(k). Examination of these TCR transgenic mice on an H-2(k/k) background that expressed the nonstimulatory s allele of murine hemoglobin revealed that these mice express many endogenous TCR chains from both α and β loci. We found that this transgenic TCR is also very inefficient at mediating β selection, thereby showing a direct linkage between β selection and allelic exclusion of TCR β. We have also examined these mice on MHC backgrounds that have reduced levels of I-E(k) and found that positive selection of cells with high levels of the transgenic TCR depends greatly on the ligand density. Decreasing the selecting ligand density is a means of reducing the number of available selecting niches, and the data reveal that the 3.L2 TCR is used sparingly for positive selection under conditions where the number of niches becomes limiting. The results, therefore, show a way that T cells may get to the periphery with two self- restricted TCRs: one that efficiently mediates positive selection, and another that is inefficient at positive selection with the available niches.